Intrascleral shunt placement

ABSTRACT

Glaucoma can be treated by implanting an intraocular shunt into an eye. The eye has an anterior chamber and sclera. A shunt can be placed into the eye to establish fluid communication from the anterior chamber of the eye through the sclera, and a pharmaceutical or biological agent can be administered to the eye.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/141,702, filed Sep. 25, 2018, which is a continuation of U.S. patentapplication Ser. No. 15/158,368, filed May 18, 2016, now U.S. Pat. No.10,080,682, which is a continuation-in-part of U.S. patent applicationSer. No. 15/005,954, filed Jan. 25, 2016, now U.S. Pat. No. 9,883,969,which is a continuation of U.S. patent application Ser. No. 14/508,938,filed Oct. 7, 2014, now U.S. Pat. No. 9,271,869, which is a continuationof U.S. patent application Ser. No. 13/314,939, filed Dec. 8, 2011, nowU.S. Pat. No. 8,852,136; U.S. patent application Ser. No. 15/158,368 isalso a continuation-in-part of U.S. patent application Ser. No.13/778,873, filed Feb. 27, 2013, now U.S. Pat. No. 9,610,195; U.S.patent application Ser. No. 15/158,368 is also a continuation of U.S.patent application Ser. No. 14/317,676, filed Jun. 27, 2014, now U.S.Pat. No. 9,808,373, which claims the priority benefit of U.S.Provisional patent application Ser. No. 61/841,224, filed on Jun. 28,2013, and U.S. Provisional patent application No. 61/895,341, filed onOct. 24, 2013; the entirety of each of which is incorporated byreference herein.

FIELD OF THE INVENTIONS

The present inventions generally relate to devices for reducingintraocular pressure by creating a drainage pathway between the anteriorchamber of the eye and the intrascleral space.

BACKGROUND

Glaucoma is a disease in which the optic nerve is damaged, leading toprogressive, irreversible loss of vision. It is typically associatedwith increased pressure of the fluid (i.e., aqueous humor) in the eye.Untreated glaucoma leads to permanent damage of the optic nerve andresultant visual field loss, which can progress to blindness. Once lost,this damaged visual field cannot be recovered. Glaucoma is the secondleading cause of blindness in the world, affecting 1 in 200 people underthe age of fifty, and 1 in 10 over the age of eighty for a total ofapproximately 70 million people worldwide.

The importance of lowering intraocular pressure (IOP) in delayingglaucomatous progression has been well documented. When drug therapyfails, or is not tolerated, surgical intervention is warranted. Surgicalfiltration methods for lowering intraocular pressure by creating a fluidflow-path between the anterior chamber and the subconjunctival tissuehave been described. One particular ab interno glaucoma filtrationmethod has been described whereby an intraocular shunt is implanted bydirecting a needle which holds the shunt through the cornea, across theanterior chamber, and through the trabecular meshwork and sclera, andinto the subconjunctival space. See, for example, U.S. Pat. No.6,544,249, U.S. Patent Pub. No. 2008/0108933, and U.S. Pat. No.6,007,511.

Proper positioning of a shunt in the subconjunctival space is criticalin determining the success or failure of subconjunctival glaucomafiltration surgery for a number of reasons. In particular, the locationof the shunt has been shown to play a role in stimulating the formationof active drainage structures such as veins or lymph vessels. See, forexample, U.S. Patent Pub. No. 2008/0108933. In addition, it has beensuggested that the conjunctiva itself plays a critical role in glaucomafiltration surgery. A healthy conjunctiva allows drainage channels toform and less opportunity for inflammation and scar tissue formation,which are frequent causes of failure in subconjunctival filtrationsurgery. See, for example, Yu et al., Progress in Retinal and EyeResearch, 28: 303-328 (2009).

SUMMARY

According to some embodiments, methods and devices are provided forpositioning an intraocular shunt within the eye to treat glaucoma.Various methods are disclosed herein which allow a clinician to create afluid pathway from the anterior chamber to an area of lower pressurewithin the eye. Although methods may be discussed in the context ofpositioning an outflow end of a shunt in a particular location (e.g.,between layers of Tenon's capsule), the methods disclosed herein can beused to create a fluid pathway in which the outflow end of the shunt ispositioned in other areas of low pressure, such as the supraciliaryspace, suprachoroidal space, the intrascleral space (i.e., betweenlayers of sclera), intra-Tenon's adhesion space (i.e., between layers ofTenon's capsule), or subconjunctival space.

In some embodiments, the present inventions also provide methods forimplanting intraocular shunts in the intrascleral space. For example, insome embodiments, methods can be performed to avoid contact between theshunt and/or delivery device with the conjunctiva. Intrascleral shuntplacement safeguards the integrity of the conjunctiva to allowsubconjunctival drainage pathways to successfully form. Additionally,the intrascleral space is less prone to fibrosis than thesubconjunctival space and placement in the intrascleral space eliminatesthe risk of hypotony and related side effects.

Methods of some embodiments involve inserting into the eye a hollowshaft configured to hold an intraocular shunt, deploying the shunt fromthe hollow shaft such that the shunt forms a passage from the anteriorchamber of the eye to the intrascleral space of the eye, and withdrawingthe hollow shaft from the eye. The implanted shunt allows drainage ofaqueous humor from an anterior chamber of the eye into the episcleralvessel complex, a traditional fluid drainage channel. Such placementalso allows diffusion of fluid into the subconjunctival andsuprachoroidal spaces.

The intraocular shunts used with methods of some embodiments define ahollow body including an inlet and an outlet, and the hollow body isconfigured to form a passage from the anterior chamber of the eye to theintrascleral space. In particular, the hollow body has a lengthsufficient to provide a passageway between the anterior chamber and theintrascleral space.

In certain aspects, some embodiments generally provide shunts composedof a material that has an elasticity modulus that is compatible with anelasticity modulus of tissue surrounding the shunt. In this manner,shunts of some embodiments are flexibility matched with the surroundingtissue, and thus will remain in place after implantation without theneed for any type of anchor that interacts with the surrounding tissue.Consequently, shunts of some embodiments will maintain fluid flow awayfor an anterior chamber of the eye after implantation without causingirritation or inflammation to the tissue surrounding the eye.

In other aspects, some embodiments generally provide shunts in which aportion of the shunt is composed of a flexible material that is reactiveto pressure, i.e., an inner diameter of the shunt fluctuates dependingupon the pressures exerted on that portion of the shunt. Thus, theflexible portion of the shunt acts as a valve that regulates fluid flowthrough the shunt. After implantation, intraocular shunts have pressureexerted upon them by tissues surrounding the shunt (e.g., scleraltissue) and pressure exerted upon them by aqueous humor flowing throughthe shunt. When the pressure exerted on the flexible portion of theshunt by the surrounding tissue is greater than the pressure exerted onthe flexible portion of the shunt by the fluid flowing through theshunt, the flexible portion decreases in diameter, restricting flowthrough the shunt. The restricted flow results in aqueous humor leavingthe anterior chamber at a reduced rate.

When the pressure exerted on the flexible portion of the shunt by thefluid flowing through the shunt is greater than the pressure exerted onthe flexible portion of the shunt by the surrounding tissue, theflexible portion increases in diameter, increasing flow through theshunt. The increased flow results in aqueous humor leaving the anteriorchamber at an increased rate.

The flexible portion of the shunt may be any portion of the shunt. Incertain embodiments, the flexible portion is a distal portion of theshunt. In certain embodiments, the entire shunt is composed of theflexible material.

Other aspects of some embodiments generally provide multi-port shunts.Such shunts reduce probability of the shunt clogging after implantationbecause fluid can enter or exit the shunt even if one or more ports ofthe shunt become clogged with particulate. In certain embodiments, theshunt includes a hollow body defining a flow path and more than twoports, in which the body is configured such that a proximal portionreceives fluid from the anterior chamber of an eye and a distal portiondirects the fluid to a location of lower pressure with respect to theanterior chamber.

The shunt may have many different configurations. In certainembodiments, the proximal portion of the shunt (i.e., the portiondisposed within the anterior chamber of the eye) includes more than oneport and the distal portion of the shunt (i.e., the portion that islocated in the intrascleral space) includes a single port. In otherembodiments, the proximal portion includes a single port and the distalportion includes more than one port. In still other embodiments, theproximal and the distal portions include more than one port.

The ports may be positioned in various different orientations and alongvarious different portions of the shunt. In certain embodiments, atleast one of the ports is oriented at an angle to the length of thebody. In certain embodiments, at least one of the ports is oriented 90°to the length of the body.

The ports may have the same or different inner diameters. In certainembodiments, at least one of the ports has an inner diameter that isdifferent from the inner diameters of the other ports.

Other aspects of some embodiments generally provide shunts with overflowports. Those shunts are configured such that the overflow port remainsclosed until there is a pressure build-up within the shunt sufficient toforce open the overflow port. Such pressure build-up typically resultsfrom particulate partially or fully clogging an entry or an exit port ofthe shunt. Such shunts reduce probability of the shunt clogging afterimplantation because fluid can enter or exit the shunt by the overflowport even if one port of the shunt becomes clogged with particulate.

In certain embodiments, the shunt includes a hollow body defining aninlet configured to receive fluid from an anterior chamber of the eyeand an outlet configured to direct the fluid to a location of lowerpressure with respect to the anterior chamber, the body furtherincluding at least one slit. The slit may be located at any place alongthe body of the shunt. In certain embodiments, the slit is located inproximity to the inlet. In other embodiments, the slit is located inproximity to the outlet. In certain embodiments, there is a slit inproximity to both the inlet and the outlet of the shunt.

In certain embodiments, the slit has a width that is substantially thesame or less than an inner diameter of the inlet. In other embodiments,the slit has a width that is substantially the same or less than aninner diameter of the outlet. Generally, the slit does not direct thefluid unless the outlet is obstructed. However, the shunt may beconfigured such that the slit does direct at least some of the fluideven if the inlet or outlet is not obstructed.

In other aspects, some embodiments generally provide a shunt having avariable inner diameter. In some embodiments, the diameter increasesfrom inlet to outlet of the shunt. By having a variable inner diameterthat increases from inlet to outlet, a pressure gradient is produced andparticulate that may otherwise clog the inlet of the shunt is forcedthrough the inlet due to the pressure gradient. Further, the particulatewill flow out of the shunt because the diameter only increases after theinlet.

In certain embodiments, the shunt includes a hollow body defining a flowpath and having an inlet configured to receive fluid from an anteriorchamber of an eye and an outlet configured to direct the fluid to theintrascleral space, in which the body further includes a variable innerdiameter that increases along the length of the body from the inlet tothe outlet. In certain embodiments, the inner diameter continuouslyincreases along the length of the body. In other embodiments, the innerdiameter remains constant along portions of the length of the body. Theshunts discussed above and herein are described relative to the eye and,more particularly, in the context of treating glaucoma and solving theabove identified problems relating to intraocular shunts. Nonetheless,it will be appreciated that shunts described herein may find applicationin any treatment of a body organ requiring drainage of a fluid from theorgan and are not limited to the eye.

In other aspects, some embodiments generally provide shunts forfacilitating conduction of fluid flow away from an organ, the shuntincluding a body, in which at least one end of the shunt is shaped tohave a plurality of prongs. Such shunts reduce probability of the shuntclogging after implantation because fluid can enter or exit the shunt byany space between the prongs even if one portion of the shunt becomesclogged with particulate.

The shunt may have many different configurations. In certainembodiments, the proximal end of the shunt (i.e., the portion disposedwithin the anterior chamber of the eye) is shaped to have the pluralityof prongs. In other embodiments, the distal end of the shunt (i.e., theportion that is located in an area of lower pressure with respect to theanterior chamber such as the intrascleral space) is shaped to have theplurality of prongs. In other embodiments, both a proximal end and adistal end of the shunt are shaped to have the plurality of prongs. Insome embodiments, the shunt is a soft gel shunt.

In other aspects, some embodiments generally provide a shunt fordraining fluid from an anterior chamber of an eye that includes a hollowbody defining an inlet configured to receive fluid from an anteriorchamber of the eye and an outlet configured to direct the fluid to alocation of lower pressure with respect to the anterior chamber; theshunt being configured such that at least one end of the shunt includesa longitudinal slit. Such shunts reduce probability of the shuntclogging after implantation because the end(s) of the shunt can moreeasily pass particulate which would generally clog a shunt lacking theslits.

The shunt may have many different configurations. In certainembodiments, the proximal end of the shunt (i.e., the portion disposedwithin the anterior chamber of the eye) includes a longitudinal slit. Inother embodiments, the distal end of the shunt (i.e., the portion thatis located in an area of lower pressure with respect to the anteriorchamber such as intrascleral space) includes a longitudinal slit. Inother embodiments, both a proximal end and a distal end of the shuntincludes a longitudinal slit. In some embodiments, the shunt is a softgel shunt.

In certain embodiments, shunts of some embodiments may be coated orimpregnated with at least one pharmaceutical and/or biological agent ora combination thereof. The pharmaceutical and/or biological agent maycoat or impregnate an entire exterior of the shunt, an entire interiorof the shunt, or both. Alternatively, the pharmaceutical and/orbiological agent may coat and/or impregnate a portion of an exterior ofthe shunt, a portion of an interior of the shunt, or both. Methods ofcoating and/or impregnating an intraocular shunt with a pharmaceuticaland/or biological agent are known in the art. See for example, Darouiche(U.S. U.S. Pat. Nos. 7,790,183; 6,719,991; 6,558,686; 6,162,487;5,902,283; 5,853,745; and 5,624,704) and Yu et al. (U.S. Patent Pub. No.2008/0108933). The content of each of these references is incorporatedby reference herein its entirety.

In certain embodiments, the exterior portion of the shunt that residesin the anterior chamber after implantation (e.g., about 1 mm of theproximal end of the shunt) is coated and/or impregnated with thepharmaceutical or biological agent. In other embodiments, the exteriorof the shunt that resides in the scleral tissue after implantation ofthe shunt is coated and/or impregnated with the pharmaceutical orbiological agent. In other embodiments, the exterior portion of theshunt that resides in the area of lower pressure (e.g., the intrascleralspace) after implantation is coated and/or impregnated with thepharmaceutical or biological agent. In embodiments in which thepharmaceutical or biological agent coats and/or impregnates the interiorof the shunt, the agent may be flushed through the shunt and into thearea of lower pressure (e.g., the intrascleral space).

Any pharmaceutical and/or biological agent or combination thereof may beused with shunts of some embodiments. The pharmaceutical and/orbiological agent may be released over a short period of time (e.g.,seconds) or may be released over longer periods of time (e.g., days,weeks, months, or even years). Exemplary agents include anti-mitoticpharmaceuticals such as Mitomycin-C or 5-Fluorouracil, anti-VEGF (suchas Lucintes, Macugen, Avastin, VEGF or steroids).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 provides a cross-sectional diagram of the general anatomy of theeye.

FIG. 2 provides another cross-sectional view the eye, and certainanatomical structures of the eye along with an implanted intraocularshunt.

FIG. 3 depicts, implantation of an intraocular shunt with a distal endof a deployment device holding a shunt, shown in cross-section.

FIG. 4 depicts an example of a hollow shaft configured to hold anintraocular shunt.

FIG. 5A depicts the tip bevel portion of a triple-ground needle tip.FIG. 5B depicts the flat bevel portion of a triple-ground needle tip.FIG. 5C depicts an intraocular shunt within a triple-ground needle tip.

FIG. 6 provides a schematic of a shunt having a flexible portion.

FIGS. 7A, 7B and 7C provide schematics of a shunt implanted into an eyefor regulation of fluid flow from the anterior chamber of the eye to adrainage structure of the eye.

FIGS. 8A-8C show different embodiments of multi-port shunts. FIG. 8Ashows an embodiment of a shunt in which the proximal portion of theshunt includes more than one port and the distal portion of the shuntincludes a single port. FIG. 8B shows another embodiment of a shunt inwhich the proximal portion includes a single port and the distal portionincludes more than one port. FIG. 8C shows another embodiment of a shuntin which the proximal portions include more than one port and the distalportions include more than one port.

FIGS. 9A and 9B show different embodiments of multi-port shunts havingdifferent diameter ports.

FIGS. 10A-10C provide schematics of shunts having a slit located along aportion of the length of the shunt.

FIG. 11 depicts a shunt having multiple slits along a length of theshunt.

FIG. 12 depicts a shunt having a slit at a proximal end of the shunt.

FIG. 13 provides a schematic of a shunt that has a variable innerdiameter.

FIGS. 14A-14D depict a shunt having multiple prongs at a distal and/orproximal end.

FIGS. 15A-15D depict a shunt having a longitudinal slit at a distaland/or proximal end.

FIG. 16 is a schematic showing an embodiment of a shunt deploymentdevice according to some embodiments.

FIG. 17 shows an exploded view of the device shown in FIG. 16.

FIGS. 18A-18D are schematics showing different enlarged views of thedeployment mechanism of the deployment device.

FIGS. 19A-19C are schematics showing interaction of the deploymentmechanism with a portion of the housing of the deployment device.

FIG. 20 shows a cross sectional view of the deployment mechanism of thedeployment device.

FIGS. 21A and 21B show schematics of the deployment mechanism in apre-deployment configuration. FIG. 21C shows an enlarged view of thedistal portion of the deployment device of FIG. 21A. This figure showsan intraocular shunt loaded within a hollow shaft of the deploymentdevice.

FIGS. 22A and 22B show schematics of the deployment mechanism at the endof the first stage of deployment of the shunt from the deploymentdevice. FIG. 22C shows an enlarged view of the distal portion of thedeployment device of FIG. 22A. This figure shows an intraocular shuntpartially deployed from within a hollow shaft of the deployment device.

FIG. 23A shows a schematic of the deployment device after deployment ofthe shunt from the device. FIG. 23B show a schematic of the deploymentmechanism at the end of the second stage of deployment of the shunt fromthe deployment device. FIG. 23C shows an enlarged view of the distalportion of the deployment device after retraction of the shaft with thepusher abutting the shunt. FIG. 23D shows an enlarged view of the distalportion of the deployment device after deployment of the shunt.

FIGS. 24-31 depict a sequence for ab interno shunt placement, accordingto some embodiments.

FIG. 32 depicts an implanted shunt in an S-shaped scleral passageway,according to some embodiments.

FIGS. 33-39 depict a sequence for ab externo shunt placement, accordingto some embodiments.

FIGS. 40-41 depict a sequence for ab externo insertion of a shaft of adeployment device using an applicator, according to some embodiments.

FIG. 42 depicts deployment of the shunt in the intra scleral space wherea distal end of the shunt is flush with the sclera surface, according tosome embodiments.

FIG. 43 depicts deployment of the shunt in the intra scleral space wherea distal end of the shunt is about 200-500 microns behind the scleralexit, according to some embodiments.

FIG. 44 depicts deployment of the shunt in the intra scleral space wherea distal end of the shunt is more than about 500 microns behind thescleral exit, according to some embodiments.

DETAILED DESCRIPTION

FIG. 1 provides a schematic diagram of the general anatomy of the eye.An anterior aspect of the anterior chamber 1 of the eye is the cornea 2,and a posterior aspect of the anterior chamber 1 of the eye is the iris4. Beneath the iris 4 is the lens 5. The anterior chamber 1 is filledwith aqueous humor 3. The aqueous humor 3 drains into a space(s) 6 belowthe conjunctiva 7 through the trabecular meshwork (not shown in detail)of the sclera 8. The aqueous humor is drained from the space(s) 6 belowthe conjunctiva 7 through a venous drainage system (not shown).

FIG. 2 provides a cross-sectional view of a portion of the eye, andprovides greater detail regarding certain anatomical structures of theeye. In particular, FIG. 2 shows a shunt 12 implanted in the sclera 8(i.e., intrascleral implantation). Placement of shunt 12 within thesclera 8 allows aqueous humor 3 to drain into traditional fluid drainagechannels of the eye (e.g., the intrascleral vein 9, the collectorchannel 10, Schlemm's canal 11, the trabecular outflow 13 a, and theuveoscleral outflow 13 b to the ciliary muscle 14.

In conditions of glaucoma, the pressure of the aqueous humor in the eye(anterior chamber) increases and this resultant increase of pressure cancause damage to the vascular system at the back of the eye andespecially to the optic nerve. The treatment of glaucoma and otherdiseases that lead to elevated pressure in the anterior chamber involvesrelieving pressure within the anterior chamber to a normal level.

Glaucoma filtration surgery is a surgical procedure typically used totreat glaucoma. The procedure involves placing a shunt in the eye torelieve intraocular pressure by creating a pathway for draining aqueoushumor from the anterior chamber of the eye. The shunt is typicallypositioned in the eye such that it creates a drainage pathway betweenthe anterior chamber of the eye and a region of lower pressure. Variousstructures and/or regions of the eye having lower pressure that havebeen targeted for aqueous humor drainage include Schlemm's canal, thesubconjunctival space, the episcleral vein, the suprachoroidal space, orthe subarachnoid space. Methods of implanting intraocular shunts areknown in the art. Shunts may be implanted using an ab externo approach(entering through the conjunctiva and inwards through the sclera) or anab interno approach (entering through the cornea, across the anteriorchamber, through the trabecular meshwork and sclera).

Ab interno approaches for implanting an intraocular shunt in thesubconjunctival space are shown for example in Yu et al. (U.S. Pat. No.6,544,249 and U.S. patent publication number 2008/0108933) and Prywes(U.S. Pat. No. 6,007,511), the contents of each of which areincorporated by reference herein in its entirety. Briefly and withreference to FIG. 3, a surgical intervention to implant the shuntinvolves inserting into the eye a deployment device 15 that holds anintraocular shunt, and deploying the shunt within the eye 16. Adeployment device 15 holding the shunt enters the eye 16 through thecornea 17 (ab interno approach). The deployment device 15 is advancedacross the anterior chamber 20 (as depicted by the broken line) in whatis referred to as a transpupil implant insertion. The deployment device15 is advanced through the sclera 21 until a distal portion of thedevice is in proximity to the subconjunctival space. The shunt is thendeployed from the deployment device, producing a conduit between theanterior chamber and the subconjunctival space to allow aqueous humor todrain through the conjunctival lymphatic system.

While such ab interno subconjunctival filtration procedures have beensuccessful in relieving intraocular pressure, there is a substantialrisk that the intraocular shunt may be deployed too close to theconjunctiva, resulting in irritation and subsequent inflammation and/orscarring of the conjunctiva, which can cause the glaucoma filtrationprocedure to fail (See Yu et al., Progress in Retinal and Eye Research,28: 303-328 (2009)). Additionally, commercially available shunts thatare currently utilized in such procedures are not ideal for ab internosubconjunctival placement due to the length of the shunt (i.e., toolong) and/or the materials used to make the shunt (e.g., gold, polymer,titanium, or stainless steel), and can cause significant irritation tothe tissue surrounding the shunt, as well as the conjunctiva, ifdeployed too close.

Some embodiments of the present inventions provide methods forimplanting intraocular shunts within the sclera (i.e., intrascleralimplantation) and are thus suitable for use in an ab interno glaucomafiltration procedure. In methods of some embodiments, the implantedshunt forms a passage from the anterior chamber of the eye into thesclera (i.e., intrascleral space). Design and/or deployment of anintraocular shunt such that the inlet terminates in the anterior chamberand the outlet terminates intrascleral safeguards the integrity of theconjunctiva to allow subconjunctival drainage pathways to successfullyform. Additionally, drainage into the intrascleral space provides accessto more lymphatic channels than just the conjunctival lymphatic system,such as the episcleral lymphatic network. Moreover, design and/ordeployment of an intraocular shunt such that the outlet terminates inthe intrascleral space avoids having to pierce Tenon's capsule which canotherwise cause complications during glaucoma filtration surgery due toits tough and fibrous nature.

Methods for Intrascleral Shunt Placement

The methods of some embodiments involve inserting into the eye a hollowshaft configured to hold an intraocular shunt. In certain embodiments,the hollow shaft is a component of a deployment device that may deploythe intraocular shunt. The shunt is then deployed from the shaft intothe eye such that the shunt forms a passage from the anterior chamberinto the sclera (i.e., the intrascleral space). The hollow shaft is thenwithdrawn from the eye.

Referring to FIG. 2, which show an intraocular shunt placed into the eyesuch that the shunt forms a passage for fluid drainage from the anteriorchamber to the intrascleral space. To place the shunt within the eye, asurgical intervention to implant the shunt is performed that involvesinserting into the eye a deployment device that holds an intraocularshunt, and deploying at least a portion of the shunt within intrascleralspace. In certain embodiments, a hollow shaft of a deployment deviceholding the shunt enters the eye through the cornea (ab internoapproach). The shaft is advanced across the anterior chamber in what isreferred to as a transpupil implant insertion. The shaft is advancedinto the sclera 8 until a distal portion of the shaft is in proximity tothe trabecular outflow 13 b. Insertion of the shaft of the deploymentdevice into the sclera 8 produces a long scleral channel of about 3 mmto about 5 mm in length. Withdrawal of the shaft of the deploymentdevice prior to deployment of the shunt 12 from the device produces aspace in which the shunt 12 may be deployed. Deployment of the shunt 12allows for aqueous humor 3 to drain into traditional fluid drainagechannels of the eye (e.g., the intrascleral vein 9, the collectorchannel 10, Schlemm's canal 11, the trabecular outflow 13 a, and theuveoscleral outflow 13 b to the ciliary muscle 14.

FIG. 4 provides an exemplary schematic of a hollow shaft for use inaccordance with the methods of some embodiments of the methods disclosedherein. This figure shows a hollow shaft 22 that is configured to holdan intraocular shunt 23. The shaft may hold the shunt within the hollowinterior 24 of the shaft, as is shown in FIG. 4. Alternatively, thehollow shaft may hold the shunt on an outer surface 25 of the shaft. Insome embodiments, the shunt is held completely within the hollowinterior of the shaft 24, as is shown in FIG. 4. In other embodiments, ashunt 23 a is only partially disposed within a hollow shaft 23 b, asshown in FIG. 5A. Generally, in one embodiment, the intraocular shuntsare of a cylindrical shape and have an outside cylindrical wall and ahollow interior. The shunt may have an inside diameter of about 10 μm toabout 250 μm, an outside diameter of about 100 μm to about 450 μm, and alength of about 1 mm to about 12 mm. In some embodiments, the shunt hasa length of about 2 mm to about 10 mm and an outside diameter of about150 μm to about 400 μm. The hollow shaft 22 is configured to at leasthold a shunt of such shape and such dimensions. However, the hollowshaft 22 may be configured to hold shunts of different shapes anddifferent dimensions than those described above, and some embodimentscan encompass a shaft 22 that may be configured to hold any shaped ordimensioned intraocular shunt.

Preferably, the methods of some embodiments are conducted by making anincision in the eye prior to insertion of the deployment device.Although in some embodiments, the methods of some embodiments may beconducted without making an incision in the eye prior to insertion ofthe deployment device. In certain embodiments, the shaft that isconnected to the deployment device has a sharpened point or tip. Incertain embodiments, the hollow shaft is a needle. Exemplary needlesthat may be used are commercially available from Terumo Medical Corp.(Elkington, Md.). In some embodiments, the needle has a hollow interiorand a beveled tip, and the intraocular shunt is held within the hollowinterior of the needle. In some embodiments, the needle has a hollowinterior and a triple ground point or tip.

The methods of some embodiments are preferably conducted without needingto remove an anatomical portion or feature of the eye, including but notlimited to the trabecular meshwork, the iris, the cornea, or aqueoushumor. The methods of some embodiments are also preferably conductedwithout inducing substantial ocular inflammation, such assubconjunctival blebbing or endophthalmitis. Such methods can beachieved using an ab interno approach by inserting the hollow shaftconfigured to hold the intraocular shunt through the cornea, across theanterior chamber, through the trabecular meshwork and into the sclera.However, the methods of some embodiments may be conducted using an abexterno approach.

Some embodiments of the methods disclosed herein can be performed suchthat the inserting step can further comprise the step of injecting anaqueous solution into the eye. For example, an aqueous solution can beinjected below Tenon's capsule. The inserting step can also comprise abinterno insertion of the hollow shaft into the eye. Ab interno insertioncan comprise inserting the hollow shaft into the eye above the corneallimbus. Ab interno insertion can comprise inserting the hollow shaftinto the eye below the corneal limbus.

For example, when the methods of some embodiments are conducted using anab interno approach, the angle of entry through the cornea affectsoptimal placement of the shunt in the intrascleral space. Preferably,the hollow shaft is inserted into the eye at an angle above or below thecorneal limbus, in contrast with entering through the corneal limbus.For example, the hollow shaft is inserted approximately 0.25 to 3.0 mm,preferably approximately 0.5 to 2.5 mm, more preferably approximately1.0 mm to 2.0 mm above the corneal limbus, or any specific value withinsaid ranges, e.g., approximately 1.0 mm, approximately 1.1 mm,approximately 1.2 mm, approximately 1.3 mm, approximately 1.4 mm,approximately 1.5 mm, approximately 1.6 mm, approximately 1.7 mm,approximately 1.8 mm, approximately 1.9 mm or approximately 2.0 mm abovethe corneal limbus.

Without intending to be bound by any theory, placement of the shuntfarther from the limbus at the exit site, as provided by an angle ofentry above the limbus, is believed to provide access to more lymphaticchannels for drainage of aqueous humor, such as the episcleral lymphaticnetwork, in addition to the conjunctival lymphatic system. A higherangle of entry also results in flatter placement in the intrascleralspace so that there is less bending of the shunt.

In certain embodiments, to ensure proper positioning and functioning ofthe intraocular shunt, the depth of penetration into the sclera isimportant when conducting the methods of some embodiments. In oneembodiment, the distal tip of the hollow shaft pierces the sclerawithout coring, removing or causing major tissue distortion of thesurrounding eye tissue. The shunt is then deployed from the shaft.Preferably, a distal portion of the hollow shaft (as opposed to thedistal tip) completely enters the sclera before the shunt is deployedfrom the hollow shaft. In certain embodiments, the hollow shaft is aflat bevel needle, such as a needle having a triple-ground point. Thetip bevel first pierces through the sclera making a horizontal slit. Ina preferred embodiment of the methods of some embodiments, the needle isadvanced even further such that the entire flat bevel penetrates intothe sclera, to spread and open the tissue to a full circular diameter.The tip bevel portion 190 and flat bevel portion 192 of a triple groundneedle point, and the configuration of the shunt 194 disposed in theneedle point, are exemplified as the gray shaded areas in FIGS. 5A-5C.Without intending to be bound by any theory, if the scleral channel isnot completely forced open by the flat bevel portion of the needle, thematerial around the opening may not be sufficiently stretched and apinching of the implant in that zone will likely occur, causing theshunt to fail. Full entry of the flat bevel into the sclera causes minordistortion and trauma to the local area. However, this area ultimatelysurrounds and conforms to the shunt once the shunt is deployed in theeye.

Intraocular Shunts

Some embodiments of the present inventions provide intraocular shuntsthat are configured to form a drainage pathway from the anterior chamberof the eye to the intrascleral space. In particular, the intraocularshunts of some embodiments have a length that is sufficient to form adrainage pathway from the anterior chamber of the eye to theintrascleral space. The length of the shunt is important for achievingplacement specifically in the intrascleral space. A shunt that is toolong will extend beyond the intrascleral space and irritate theconjunctiva which can cause the filtration procedure to fail, aspreviously described. A shunt that is too short will not providesufficient access to drainage pathways such as the episcleral lymphaticsystem or the conjunctival lymphatic system.

Shunts of some embodiments may be any length that allows for drainage ofaqueous humor from an anterior chamber of an eye to the intrascleralspace. Exemplary shunts range in length from approximately 2 mm toapproximately 10 mm or between approximately 4 mm to approximately 8 mm,or any specific value within said ranges. In certain embodiments, thelength of the shunt is between approximately 6 to 8 mm, or any specificvalue within said range, e.g., 6.0 mm, 6.1 mm, 6.2 mm, 6.3 mm, 6.4 mm,6.5 mm, 6.6 mm, 6.7 mm, 6.8 mm, 6.9 mm, 7 mm, 7.1 mm, 7.2 mm, 7.3 mm,7.4 mm, 7.5 mm, 7.6 mm, 7.7 mm, 7.8 mm. 7.9 mm, or 8.0 mm.

The intraocular shunts of some embodiments are particularly suitable foruse in an ab interno glaucoma filtration procedure. Commerciallyavailable shunts that are currently used in ab interno filtrationprocedures are typically made of a hard, inflexible material such asgold, polymer, titanium, or stainless steel, and cause substantialirritation of the eye tissue, resulting in ocular inflammation such assubconjunctival blebbing or endophthalmitis. The methods of someembodiments may be conducted using any commercially available shunts,such as the Optonol Ex-PRESS™ mini Glaucoma shunt, and the SolxDeepLight Gold™ Micro-Shunt.

In some embodiments, the intraocular shunts of some embodiments areflexible, and have an elasticity modulus that is substantially identicalto the elasticity modulus of the surrounding tissue in the implant site.As such, the intraocular shunts of some embodiments are easily bendable,do not erode or cause a tissue reaction, and do not migrate onceimplanted. Thus, when implanted in the eye using an ab internoprocedure, such as the methods described herein, the intraocular shuntsof some embodiments do not induce substantial ocular inflammation suchas subconjunctival blebbing or endophthalmitis. Additional exemplaryfeatures of the intraocular shunts of some embodiments are discussed infurther detail below.

Tissue Compatible Shunts

In certain aspects, some embodiments generally provide shunts composedof a material that has an elasticity modulus that is compatible with anelasticity modulus of tissue surrounding the shunt. In this manner,shunts of some embodiments are flexibility matched with the surroundingtissue, and thus will remain in place after implantation without theneed for any type of anchor that interacts with the surrounding tissue.Consequently, shunts of some embodiments will maintain fluid flow awayfor an anterior chamber of the eye after implantation without causingirritation or inflammation to the tissue surrounding the eye.

Elastic modulus, or modulus of elasticity, is a mathematical descriptionof an object or substance's tendency to be deformed elastically when aforce is applied to it. The elastic modulus of an object is defined asthe slope of its stress-strain curve in the elastic deformation region:

$\lambda\overset{def}{=}\frac{Stress}{Strain}$

where lambda (λ) is the elastic modulus; stress is the force causing thedeformation divided by the area to which the force is applied; andstrain is the ratio of the change caused by the stress to the originalstate of the object. The elasticity modulus may also be known as Young'smodulus (E), which describes tensile elasticity, or the tendency of anobject to deform along an axis when opposing forces are applied alongthat axis. Young's modulus is defined as the ratio of tensile stress totensile strain. For further description regarding elasticity modulus andYoung's modulus, see for example Gere (Mechanics of Materials, 6^(th)Edition, 2004, Thomson), the content of which is incorporated byreference herein in its entirety.

The elasticity modulus of any tissue can be determined by one of skillin the art. See for example Samani et al. (Phys. Med. Biol. 48:2183,2003); Erkamp et al. (Measuring The Elastic Modulus Of Small TissueSamples, Biomedical Engineering Department and Electrical Engineeringand Computer Science Department University of Michigan Ann Arbor, Mich.48109-2125; and Institute of Mathematical Problems in Biology RussianAcademy of Sciences, Pushchino, Moscow Region 142292 Russia); Chen etal. (IEEE Trans. Ultrason. Ferroelec. Freq. Control 43:191-194, 1996);Hall, (In 1996 Ultrasonics Symposium Proc., pp. 1193-1196, IEEE Cat. No.96CH35993, IEEE, New York, 1996); and Parker (Ultrasound Med. Biol.16:241-246, 1990), each of which provides methods of determining theelasticity modulus of body tissues. The content of each of these isincorporated by reference herein in its entirety.

The elasticity modulus of tissues of different organs is known in theart. For example, Pierscionek et al. (Br J Ophthalmol, 91:801-803, 2007)and Friberg (Experimental Eye Research, 473:429-436, 1988) show theelasticity modulus of the cornea and the sclera of the eye. The contentof each of these references is incorporated by reference herein in itsentirety. Chen, Hall, and Parker show the elasticity modulus ofdifferent muscles and the liver. Erkamp shows the elasticity modulus ofthe kidney.

Shunts of some embodiments are composed of a material that is compatiblewith an elasticity modulus of tissue surrounding the shunt. In certainembodiments, the material has an elasticity modulus that issubstantially identical to the elasticity modulus of the tissuesurrounding the shunt. In other embodiments, the material has anelasticity modulus that is greater than the elasticity modulus of thetissue surrounding the shunt. Exemplary materials includes biocompatiblepolymers, such as polycarbonate, polyethylene, polyethyleneterephthalate, polyimide, polystyrene, polypropylene,poly(styrene-b-isobutylene-b-styrene), or silicone rubber.

In some embodiments, shunts of some embodiments are composed of amaterial that has an elasticity modulus that is compatible with theelasticity modulus of tissue in the eye, particularly scleral tissue. Incertain embodiments, compatible materials are those materials that aresofter than scleral tissue or marginally harder than scleral tissue, yetsoft enough to prohibit shunt migration. The elasticity modulus foranterior scleral tissue is approximately 2.9±1.4×10⁶ N/m², and1.8±1.1×10⁶ N/m² for posterior scleral tissue. See Friberg (ExperimentalEye Research, 473:429-436, 1988). An exemplary material is cross linkedgelatin derived from Bovine or Porcine Collagen.

Some embodiments encompass shunts of different shapes and differentdimensions, and the shunts of some embodiments may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 100 μm to approximately 450 μm, and a lengthfrom approximately 2 mm to approximately 10 mm.

Shunts Reactive to Pressure

In other aspects, some embodiments generally provide shunts in which aportion of the shunt is composed of a flexible material that is reactiveto pressure, i.e., the diameter of the flexible portion of the shuntfluctuates depending upon the pressures exerted on that portion of theshunt. FIG. 6 provides a schematic of a shunt 23 having a flexibleportion 51. In this figure, the flexible portion 51 is shown in themiddle of the shunt 23. However, the flexible portion 51 may be locatedin any portion of the shunt, such as the proximal or distal portion ofthe shunt. In certain embodiments, the entire shunt is composed of theflexible material, and thus the entire shunt is flexible and reactive topressure.

The flexible portion 51 of the shunt 23 acts as a valve that regulatesfluid flow through the shunt. The human eye produces aqueous humor at arate of about 2 μl/min for approximately 3 ml/day. The entire aqueousvolume is about 0.25 ml. When the pressure in the anterior chamber fallsafter surgery to about 7-8 mmHg, it is assumed the majority of theaqueous humor is exiting the eye through the implant since venousbackpressure prevents any significant outflow through normal drainagestructures (e.g., the trabecular meshwork).

After implantation, intraocular shunts have pressure exerted upon themby tissues surrounding the shunt (e.g., scleral tissue such as thesclera channel and the sclera exit) and pressure exerted upon them byaqueous humor flowing through the shunt. The flow through the shunt, andthus the pressure exerted by the fluid on the shunt, is calculated bythe equation:

${\Phi = {\frac{dV}{dT} = {{v\pi R^{2}} = {{\frac{\pi R^{4}}{8\eta}\left( \frac{{- \Delta}P}{\Delta x} \right)} = \frac{\pi R^{4}}{8\eta}}}}}\frac{\left| {\Delta\; P} \right|}{L}$

where Φ is the volumetric flow rate; V is a volume of the liquid poured(cubic meters); t is the time (seconds); v is mean fluid velocity alongthe length of the tube (meters/second); x is a distance in direction offlow (meters); R is the internal radius of the tube (meters); ΔP is thepressure difference between the two ends (pascals); η is the dynamicfluid viscosity (pascal-second (Pa·s)); and L is the total length of thetube in the x direction (meters).

FIG. 7A provides a schematic of a shunt 26 implanted into an eye forregulation of fluid flow from the anterior chamber of the eye to an areaof lower pressure (e.g., the intrascleral space). The shunt is implantedsuch that a proximal end 27 of the shunt 26 resides in the anteriorchamber 28 of the eye, and a distal end 29 of the shunt 26 residesoutside of the anterior chamber to conduct aqueous humor from theanterior chamber to an area of lower pressure. A flexible portion 30 ofthe shunt 26 spans at least a portion of the sclera of the eye. As shownin FIG. 7A, the flexible portion spans an entire length of the sclera31.

When the pressure exerted on the flexible portion 30 of the shunt 26 bysclera 31 (vertical arrows) is greater than the pressure exerted on theflexible portion 30 of the shunt 26 by the fluid flowing through theshunt (horizontal arrow), the flexible portion 30 decreases in diameter,restricting flow through the shunt 26 (FIG. 7B). The restricted flowresults in aqueous humor leaving the anterior chamber 28 at a reducedrate.

When the pressure exerted on the flexible portion 30 of the shunt 26 bythe fluid flowing through the shunt (horizontal arrow) is greater thanthe pressure exerted on the flexible portion 30 of the shunt 26 by thesclera 31 (vertical arrows), the flexible portion 30 increases indiameter, increasing flow through the shunt 26 (FIG. 7C). The increasedflow results in aqueous humor leaving the anterior chamber 28 at anincreased rate.

Some embodiments encompass shunts of different shapes and differentdimensions, and the shunts of some embodiments may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 100 μm to approximately 450 μm, and a lengthfrom approximately 2 mm to approximately 10 mm.

In some embodiments, the shunt has a length of about 6 mm and an innerdiameter of about 64 μm. With these dimensions, the pressure differencebetween the proximal end of the shunt that resides in the anteriorchamber and the distal end of the shunt that resides outside theanterior chamber is about 4.3 mmHg. Such dimensions thus allow theimplant to act as a controlled valve and protect the integrity of theanterior chamber.

It will be appreciated that different dimensioned implants may be used.For example, shunts that range in length from about 2 mm to about 10 mmand have a range in inner diameter from about 10 μm to about 100 μmallow for pressure control from approximately 0.5 mmHg to approximately20 mmHg.

The material of the flexible portion and the thickness of the wall ofthe flexible portion will determine how reactive the flexible portion isto the pressures exerted upon it by the surrounding tissue and the fluidflowing through the shunt. Generally, with a certain material, thethicker the flexible portion, the less responsive the portion will be topressure. In certain embodiments, the flexible portion is a gelatin orother similar material, and the thickness of the gelatin materialforming the wall of the flexible portion ranges from about 10 μm thickto about 100 μm thick.

In a certain embodiment, the gelatin used for making the flexibleportion is known as gelatin Type B from bovine skin. An exemplarygelatin is PB Leiner gelatin from bovine skin, Type B, 225 Bloom, USP.Another material that may be used in the making of the flexible portionis a gelatin Type A from porcine skin, also available from SigmaChemical. Such gelatin is available from Sigma Chemical Company of St.Louis, Mo. under Code G-9382. Still other suitable gelatins includebovine bone gelatin, porcine bone gelatin and human-derived gelatins. Inaddition to gelatins, the flexible portion may be made of hydroxypropylmethylcellulose (HPMC), collagen, polylactic acid, polylglycolic acid,hyaluronic acid and glycosaminoglycans.

In certain embodiments, the gelatin is cross-linked. Cross-linkingincreases the inter- and intramolecular binding of the gelatinsubstrate. Any method for cross-linking the gelatin may be used. In someembodiments, the formed gelatin is treated with a solution of across-linking agent such as, but not limited to, glutaraldehyde. Othersuitable compounds for cross-linking include1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC). Cross-linking byradiation, such as gamma or electron beam (e-beam) may be alternativelyemployed.

In one embodiment, the gelatin is contacted with a solution ofapproximately 25% glutaraldehyde for a selected period of time. Onesuitable form of glutaraldehyde is a grade 1G5882 glutaraldehydeavailable from Sigma Aldridge Company of Germany, although otherglutaraldehyde solutions may also be used. The pH of the glutaraldehydesolution should be in the range of 7 to 7.8 and, more particularly,7.35-7.44 and typically approximately 7.4 +/−0.01. If necessary, the pHmay be adjusted by adding a suitable amount of a base such as sodiumhydroxide as needed.

Methods for forming the flexible portion of the shunt are shown forexample in Yu et al. (U.S. Patent Pub. No. 2008/0108933), the content ofwhich is incorporated by reference herein in its entirety. In anexemplary protocol, the flexible portion may be made by dipping a coreor substrate such as a wire of a suitable diameter in a solution ofgelatin. The gelatin solution is typically prepared by dissolving agelatin powder in de-ionized water or sterile water for injection andplacing the dissolved gelatin in a water bath at a temperature ofapproximately 55° C. with thorough mixing to ensure complete dissolutionof the gelatin. In one embodiment, the ratio of solid gelatin to wateris approximately 10% to 50% gelatin by weight to 50% to 90% by weight ofwater. In an embodiment, the gelatin solution includes approximately 40%by weight, gelatin dissolved in water. The resulting gelatin solutionshould be devoid of air bubbles and has a viscosity that is betweenapproximately 200-500 cp and more particularly between approximately 260and 410 cp (centipoise).

Once the gelatin solution has been prepared, in accordance with themethod described above, supporting structures such as wires having aselected diameter are dipped into the solution to form the flexibleportion. Stainless steel wires coated with a biocompatible, lubriciousmaterial such as polytetrafluoroethylene (Teflon) are preferred.

Typically, the wires are gently lowered into a container of the gelatinsolution and then slowly withdrawn. The rate of movement is selected tocontrol the thickness of the coat. In addition, it is preferred that thetube be removed at a constant rate in order to provide the desiredcoating. To ensure that the gelatin is spread evenly over the surface ofthe wire, in one embodiment, the wires may be rotated in a stream ofcool air which helps to set the gelatin solution and affix film onto thewire. Dipping and withdrawing the wire supports may be repeated severaltimes to further ensure even coating of the gelatin. Once the wires havebeen sufficiently coated with gelatin, the resulting gelatin films onthe wire may be dried at room temperature for at least 1 hour, and morepreferably, approximately 10 to 24 hours. Apparatus for forming gelatintubes are described in Yu et al. (U.S. Patent Pub. No. 2008/0108933).

Once dried, the formed flexible portions may be treated with across-linking agent. In one embodiment, the formed flexible portion maybe cross-linked by dipping the wire (with film thereon) into the 25%glutaraldehyde solution, at pH of approximately 7.0-7.8 and morepreferably approximately 7.35-7.44 at room temperature for at least 4hours and preferably between approximately 10 to 36 hours, depending onthe degree of cross-linking desired. In one embodiment, the formedflexible portion is contacted with a cross-linking agent such asgluteraldehyde for at least approximately 16 hours. Cross-linking canalso be accelerated when it is performed a high temperature. It isbelieved that the degree of cross-linking is proportional to thebioabsorption time of the shunt once implanted. In general, the morecross-linking, the longer the survival of the shunt in the body.

The residual glutaraldehyde or other cross-linking agent is removed fromthe formed flexible portion by soaking the tubes in a volume of sterilewater for injection. The water may optionally be replaced at regularintervals, circulated or re-circulated to accelerate diffusion of theunbound glutaraldehyde from the tube. The tubes are washed for a periodof a few hours to a period of a few months with the ideal time being3-14 days. The now cross-linked gelatin tubes may then be dried (cured)at ambient temperature for a selected period of time. It has beenobserved that a drying period of approximately 48-96 hours and moretypically 3 days (i.e., 72 hours) may be preferred for the formation ofthe cross-linked gelatin tubes.

Where a cross-linking agent is used, it may be desirable to include aquenching agent in the method of making the flexible portion. Quenchingagents remove unbound molecules of the cross-linking agent from theformed flexible portion. In certain cases, removing the cross-linkingagent may reduce the potential toxicity to a patient if too much of thecross-linking agent is released from the flexible portion. In certainembodiments, the formed flexible portion is contacted with the quenchingagent after the cross-linking treatment and, may be included with thewashing/rinsing solution. Examples of quenching agents include glycineor sodium borohydride.

After the requisite drying period, the formed and cross-linked flexibleportion is removed from the underlying supports or wires. In oneembodiment, wire tubes may be cut at two ends and the formed gelatinflexible portion slowly removed from the wire support. In anotherembodiment, wires with gelatin film thereon, may be pushed off using aplunger or tube to remove the formed gelatin flexible portion.

Multi-Port Shunts

Other aspects of some embodiments generally provide multi-port shunts.Such shunts reduce probability of the shunt clogging after implantationbecause fluid can enter or exit the shunt even if one or more ports ofthe shunt become clogged with particulate. In certain embodiments, theshunt includes a hollow body defining a flow path and more than twoports, in which the body is configured such that a proximal portionreceives fluid from the anterior chamber of an eye and a distal portiondirects the fluid to drainage structures associated with theintrascleral space.

The shunt may have many different configurations. FIGS. 8A-8C shows anembodiment of a shunt 32 in which the proximal portion of the shunt(i.e., the portion disposed within the anterior chamber of the eye)includes more than one port (designated as numbers 33 a-33 e) and thedistal portion of the shunt (i.e., the portion that is located in theintrascleral space) includes a single port 34. FIG. 8B shows anotherembodiment of a shunt 32 in which the proximal portion includes a singleport 33 and the distal portion includes more than one port (designatedas numbers 34 a-34 e). FIG. 8C shows another embodiment of a shunt 32 inwhich the proximal portions include more than one port (designated asnumbers 33 a-33 e) and the distal portions include more than one port(designated as numbers 34 a-34 e). While FIGS. 8A-8C show shunts havefive ports at the proximal portion, distal portion, or both, thoseshunts are only exemplary embodiments. The ports may be located alongany portion of the shunt, and shunts of some embodiments include allshunts having more than two ports. For example, shunts of someembodiments may include at least three ports, at least four ports, atleast five ports, at least 10 ports, at least 15 ports, or at least 20ports.

The ports may be positioned in various different orientations and alongvarious different portions of the shunt. In certain embodiments, atleast one of the ports is oriented at an angle to the length of thebody. In certain embodiments, at least one of the ports is oriented 90°to the length of the body. See for example FIG. 8A, which depicts ports33 a, 33 b, 33 d, and 33 e as being oriented at a 90° angle to port 33c.

The ports may have the same or different inner diameters. In certainembodiments, at least one of the ports has an inner diameter that isdifferent from the inner diameters of the other ports. FIGS. 9A and 9Bshow an embodiment of a shunt 32 having multiple ports (33 a and 33 b)at a proximal end and a single port 34 at a distal end. FIG. 9A showsthat port 33 b has an inner diameter that is different from the innerdiameters of ports 33 a and 34. In this figure, the inner diameter ofport 33 b is less than the inner diameter of ports 33 a and 34. Anexemplary inner diameter of port 33 b is from about 20 μm to about 40μm, particularly about 30 μm. In other embodiments, the inner diameterof port 33 b is greater than the inner diameter of ports 33 a and 34.See for example FIG. 9B.

Some embodiments encompass shunts of different shapes and differentdimensions, and the shunts of some embodiments may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 100 μm to approximately 450 μm, and a lengthfrom approximately 2 mm to approximately 10 mm. Shunts of someembodiments may be made from any biocompatible material. An exemplarymaterial is gelatin. Methods of making shunts composed of gelatin aredescribed above.

Shunts with Overflow Ports

Other aspects of some embodiments generally provide shunts with overflowports. Those shunts are configured such that the overflow port remainspartially or completely closed until there is a pressure build-up withinthe shunt sufficient to force open the overflow port. Such pressurebuild-up typically results from particulate partially or fully cloggingan entry or an exit port of the shunt. Such shunts reduce probability ofthe shunt clogging after implantation because fluid can enter or exitthe shunt by the overflow port even if one port of the shunt becomesclogged with particulate.

In certain embodiments, the shunt includes a hollow body defining aninlet configured to receive fluid from an anterior chamber of an eye andan outlet configured to direct the fluid to the intrascleral space, thebody further including at least one slit. The slit may be located at anyplace along the body of the shunt. FIG. 10A shows a shunt 35 having aninlet 36, an outlet 37, and a slit 38 located in proximity to the inlet36. FIG. 10B shows a shunt 35 having an inlet 36, an outlet 37, and aslit 39 located in proximity to the outlet 37. FIG. 10C shows a shunt 35having an inlet 36, an outlet 37, a slit 38 located in proximity to theinlet 36, and a slit 39 located in proximity to the outlet 37.

While FIGS. 10A-10C show shunts have only a single overflow port at theproximal portion, the distal portion, or both the proximal and distalportions, those shunts are only exemplary embodiments. The overflowport(s) may be located along any portion of the shunt, and shunts ofsome embodiments include shunts having more than one overflow port. Incertain embodiments, shunts of some embodiments include more than oneoverflow port at the proximal portion, the distal portion, or both. Forexample, FIG. 11 shows a shunt 40 having an inlet 41, an outlet 42, andslits 43 a and 43 b located in proximity to the inlet 41. Shunts of someembodiments may include at least two overflow ports, at least threeoverflow ports, at least four overflow ports, at least five overflowports, at least 10 overflow ports, at least 15 overflow ports, or atleast 20 overflow ports. In certain embodiments, shunts of someembodiments include two slits that overlap and are oriented at 90° toeach other, thereby forming a cross.

In certain embodiments, the slit may be at the proximal or the distalend of the shunt, producing a split in the proximal or the distal end ofthe implant. FIG. 12 shows an embodiment of a shunt 44 having an inlet45, outlet 46, and a slit 47 that is located at the proximal end of theshunt, producing a split in the inlet 45 of the shunt.

In certain embodiments, the slit has a width that is substantially thesame or less than an inner diameter of the inlet. In other embodiments,the slit has a width that is substantially the same or less than aninner diameter of the outlet. In certain embodiments, the slit has alength that ranges from about 0.05 mm to about 2 mm, and a width thatranges from about 10 μm to about 200 μm. Generally, the slit does notdirect the fluid unless the outlet is obstructed. However, the shunt maybe configured such that the slit does direct at least some of the fluideven if the inlet or outlet is not obstructed.

Some embodiments encompass shunts of different shapes and differentdimensions, and the shunts of some embodiments may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 100 μm to approximately 450 and a lengthfrom approximately 2 mm to approximately 10 mm. Shunts of someembodiments may be made from any biocompatible material. An exemplarymaterial is gelatin. Methods of making shunts composed of gelatin aredescribed above.

Shunts having a Variable Inner Diameter

In other aspects, some embodiments generally provide a shunt having avariable inner diameter. In some embodiments, the diameter increasesfrom inlet to outlet of the shunt. By having a variable inner diameterthat increases from inlet to outlet, a pressure gradient is produced andparticulate that may otherwise clog the inlet of the shunt is forcedthrough the inlet due to the pressure gradient. Further, the particulatewill flow out of the shunt because the diameter only increases after theinlet.

FIG. 13 shows an embodiment of a shunt 48 having an inlet 49 configuredto receive fluid from an anterior chamber of an eye and an outlet 50configured to direct the fluid to a location of lower pressure withrespect to the anterior chamber, in which the body further includes avariable inner diameter that increases along the length of the body fromthe inlet 49 to the outlet 50. In certain embodiments, the innerdiameter continuously increases along the length of the body, forexample as shown in FIG. 13. In other embodiments, the inner diameterremains constant along portions of the length of the body.

In exemplary embodiments, the inner diameter may range in size fromabout 10 μm to about 200 μm, and the inner diameter at the outlet mayrange in size from about 15 μm to about 300 μm. Some embodimentsencompass shunts of different shapes and different dimensions, and theshunts of some embodiments may be any shape or any dimension that may beaccommodated by the eye. In certain embodiments, the intraocular shuntis of a cylindrical shape and has an outside cylindrical wall and ahollow interior. The shunt may have an inside diameter fromapproximately 10 μm to approximately 250 μm, an outside diameter fromapproximately 100 μm to approximately 450 μm, and a length fromapproximately 2 mm to approximately 10 mm. Shunts of some embodimentsmay be made from any biocompatible material. An exemplary material isgelatin. Methods of making shunts composed of gelatin are describedabove.

Shunts having Pronged Ends

In other aspects, some embodiments generally provide shunts forfacilitating conduction of fluid flow away from an organ, the shuntincluding a body, in which at least one end of the shunt is shaped tohave a plurality of prongs. Such shunts reduce probability of the shuntclogging after implantation because fluid can enter or exit the shunt byany space between the prongs even if one portion of the shunt becomesclogged with particulate.

FIGS. 14A-14D show embodiments of a shunt 52 in which at least one endof the shunt 52 includes a plurality of prongs 53 a-d. FIGS. 14A-14Dshow embodiments in which both a proximal end and a distal end of theshunt are shaped to have the plurality of prongs. However, numerousdifferent configurations are envisioned. For example, in certainembodiments, only the proximal end of the shunt is shaped to have theplurality of prongs. In other embodiments, only the distal end of theshunt is shaped to have the plurality of prongs.

Prongs 53 a-d can have any shape (i.e., width, length, height). FIGS.14A and 14B show prongs 53 a-d as straight prongs. In this embodiment,the spacing between the prongs 53 a-d is the same. In another embodimentshown in FIGS. 14C and 14D, prongs 53 a-d are tapered. In thisembodiment, the spacing between the prongs increases toward a proximaland/or distal end of the shunt 52.

FIGS. 14A-14D show embodiments that include four prongs. However, shuntsof some embodiments may accommodate any number of prongs, such as twoprongs, three prongs, four prongs, five prongs, six prongs, sevenprongs, eight prongs, nine prongs, ten prongs, etc. The number of prongschosen will depend on the desired flow characteristics of the shunt.

Some embodiments encompass shunts of different shapes and differentdimensions, and the shunts of some embodiments may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 100 μm to approximately 450 μm, and a lengthfrom approximately 2 mm to approximately 10 mm. Shunts of someembodiments may be made from any biocompatible material. An exemplarymaterial is gelatin. Methods of making shunts composed of gelatin aredescribed above.

Shunts having a Longitudinal Slit

In other aspects, some embodiments generally provide a shunt fordraining fluid from an anterior chamber of an eye that includes a hollowbody defining an inlet configured to receive fluid from an anteriorchamber of the eye and an outlet configured to direct the fluid to alocation of lower pressure with respect to the anterior chamber; theshunt being configured such that at least one end of the shunt includesa longitudinal slit. Such shunts reduce probability of the shuntclogging after implantation because the end(s) of the shunt can moreeasily pass particulate which would generally clog a shunt lacking theslits.

FIGS. 15A-15D show embodiments of a shunt 54 in which at least one endof the shunt 54 includes a longitudinal slit 55 that produces a topportion 56 a and a bottom portion 56 b in a proximal and/or distal endof the shunt 54. FIGS. 15A-15D show an embodiment in which both aproximal end and a distal end include a longitudinal slit 55 thatproduces a top portion 56 a and a bottom portion 56 b in both ends ofthe shunt 54. However, numerous different configurations are envisioned.For example, in certain embodiments, only the proximal end of the shuntincludes longitudinal slit 55. In other embodiments, only the distal endof the shunt includes longitudinal slit 55.

Longitudinal slit 55 can have any shape (i.e., width, length, height).FIGS. 15A and 15B show a longitudinal slit 55 that is straight such thatthe space between the top portion 56 a and the bottom portion 56 bremains the same along the length of the slit 55. In another embodimentshown in FIGS. 15C-15D, longitudinal slit 55 is tapered. In thisembodiment, the space between the top portion 45 a and the bottomportion 56 b increases toward a proximal and/or distal end of the shunt54.

Some embodiments encompass shunts of different shapes and differentdimensions, and the shunts of some embodiments may be any shape or anydimension that may be accommodated by the eye. In certain embodiments,the intraocular shunt is of a cylindrical shape and has an outsidecylindrical wall and a hollow interior. The shunt may have an insidediameter from approximately 10 μm to approximately 250 μm, an outsidediameter from approximately 100 μm to approximately 450 μm, and a lengthfrom approximately 2 mm to approximately 10 mm. Shunts of someembodiments may be made from any biocompatible material. An exemplarymaterial is gelatin. Methods of making shunts composed of gelatin aredescribed above.

Pharmaceutical Agents

In certain embodiments, shunts of some embodiments may be coated orimpregnated with at least one pharmaceutical and/or biological agent ora combination thereof. The pharmaceutical and/or biological agent maycoat or impregnate an entire exterior of the shunt, an entire interiorof the shunt, or both. Alternatively, the pharmaceutical or biologicalagent may coat and/or impregnate a portion of an exterior of the shunt,a portion of an interior of the shunt, or both. Methods of coatingand/or impregnating an intraocular shunt with a pharmaceutical and/orbiological agent are known in the art. See for example, Darouiche (U.S.Pat. Nos. 7,790,183; 6,719,991; 6,558,686; 6,162,487; 5,902,283;5,853,745; and 5,624,704) and Yu et al. (U.S. Patent Pub. No.2008/0108933). The content of each of these references is incorporatedby reference herein its entirety.

In certain embodiments, the exterior portion of the shunt that residesin the anterior chamber after implantation (e.g., about 1 mm of theproximal end of the shunt) is coated and/or impregnated with thepharmaceutical or biological agent. In other embodiments, the exteriorof the shunt that resides in the scleral tissue after implantation ofthe shunt is coated and/or impregnated with the pharmaceutical orbiological agent. In other embodiments, the exterior portion of theshunt that resides in the intrascleral space after implantation iscoated and/or impregnated with the pharmaceutical or biological agent.In embodiments in which the pharmaceutical or biological agent coatsand/or impregnates the interior of the shunt, the agent may be flushedthrough the shunt and into the area of lower pressure (e.g., theintrascleral space).

Any pharmaceutical and/or biological agent or combination thereof may beused with shunts of some embodiments. The pharmaceutical and/orbiological agent may be released over a short period of time (e.g.,seconds) or may be released over longer periods of time (e.g., days,weeks, months, or even years). Exemplary agents include anti-mitoticpharmaceuticals such as Mitomycin-C or 5-Fluorouracil, anti-VEGF (suchas Lucintes, Macugen, Avastin, VEGF or steroids).

Deployment Devices

Deployment into the eye of an intraocular shunt according to someembodiments can be achieved using a hollow shaft configured to hold theshunt, as described herein. The hollow shaft can be coupled to adeployment device or part of the deployment device itself. Deploymentdevices that are suitable for deploying shunts according to someembodiments include but are not limited to the deployment devicesdescribed in U.S. Pat. No. 6,007,511, U.S. Pat. No. 6,544,249, and U.S.Publication No. 2008/0108933, the contents of which are eachincorporated herein by reference in their entireties. In otherembodiments, the deployment devices are devices as described inco-pending and co-owned U.S. patent application Ser. No. 12/946,222filed on Nov. 15, 2010, or deployment devices described in co-pendingand co-owned U.S. patent application Ser. No. 12/946,645, filed on Nov.15, 2010, the entire content of each of which is incorporated byreference herein.

A shunt deployment device, such as those disclosed herein, can be usedto implant the shunt in accordance with a variety of potentialprocedures, which can be modified or updated, according to aspects ofthe disclosure herein, as well as future methodologies and devicefeatures. For example, as discussed and shown below with regard to FIGS.52A-54E of copending U.S. patent application Ser. No. 14/317,676, filedon Jun. 27, 2014, the entirety of which is incorporated herein byreference, a shunt deployment device can be used to implant a shuntusing a variety of different procedures. The deployment device can bemanual or automatic and can include features of one or more of thedevices discussed or mentioned herein.

In still other embodiments, the shunts according to some embodiments aredeployed into the eye using the deployment device 100 depicted in FIG.16. While FIG. 16 shows a handheld manually operated shunt deploymentdevice, it will be appreciated that devices of some embodiments may becoupled with robotic systems and may be completely or partiallyautomated. As shown in FIG. 16, deployment device 100 includes agenerally cylindrical body or housing 101, however, the body shape ofhousing 101 could be other than cylindrical. Housing 101 may have anergonomical shape, allowing for comfortable grasping by an operator.Housing 101 is shown with optional grooves 102 to allow for easiergripping by a surgeon.

According to some embodiments, the shunt can be advanced into the eyetissue at a rate of between about 0.15 mm/sec to about 0.85 mm/sec.Further, in some embodiments, the shunt can be advanced into the eyetissue at a rate of between about 0.25 mm/sec to about 0.65 mm/sec.

Housing 101 is shown having a larger proximal portion that tapers to adistal portion. The distal portion includes a hollow sleeve 105. Thehollow sleeve 105 is configured for insertion into an eye and to extendinto an anterior chamber of an eye. The hollow sleeve is visible withinan anterior chamber of an eye. According to some embodiment, the sleeve105 can provide a visual preview or guide for an operator as toplacement of the proximal portion of the shunt within the anteriorchamber of an eye, as discussed below with regard to FIGS. 52A-52E ofcopending U.S. patent application Ser. No. 14/317,676, filed on June 27,2014. The sleeve 105 can provide a visual reference point that may beused by an operator to hold device 100 steady during the shuntdeployment process, thereby assuring optimal longitudinal placement ofthe shunt within the eye. The sleeve 105 may include an edge at a distalend that provides resistance feedback to an operator upon insertion ofthe deployment device 100 within an eye of a person. Upon advancement ofthe device 100 across an anterior chamber of the eye, the hollow sleeve105 will eventually contact the sclera, providing resistance feedback toan operator that no further advancement of the device 100 is necessary.The edge of the sleeve 105, prevents the shaft 104 from accidentallybeing pushed too far through the sclera. A temporary guard 108 isconfigured to fit around sleeve 105 and extend beyond an end of sleeve105. The guard is used during shipping of the device and protects anoperator from a distal end of a hollow shaft 104 that extends beyond theend of the sleeve 105. The guard is removed prior to use of the device.

Housing 101 is open at its proximal end, such that a portion of adeployment mechanism 103 may extend from the proximal end of the housing101. A distal end of housing 101 is also open such that at least aportion of a hollow shaft 104 may extend through and beyond the distalend of the housing 101. Housing 101 further includes a slot 106 throughwhich an operator, such as a surgeon, using the device 100 may view anindicator 107 on the deployment mechanism 103.

Housing 101 may be made of any material that is suitable for use inmedical devices. For example, housing 101 may be made of a lightweightaluminum or a biocompatible plastic material. Examples of such suitableplastic materials include polycarbonate and other polymeric resins suchas DELRIN and ULTEM. In certain embodiments, housing 101 is made of amaterial that may be autoclaved, and thus allow for housing 101 to bere-usable. Alternatively, device 100, may be sold as a one-time-usedevice, and thus the material of the housing does not need to be amaterial that is autoclavable.

Housing 101 may be made of multiple components that connect together toform the housing. FIG. 17 shows an exploded view of deployment device100. In this figure, housing 101, is shown having three components 101a, 101 b, and 101 c. The components are designed to screw together toform housing 101. FIGS. 18A-18D also show deployment mechanism 103. Thehousing 101 is designed such that deployment mechanism 103 fits withinassembled housing 101. Housing 101 is designed such that components ofdeployment mechanism 103 are movable within housing 101.

FIGS. 18A-18D show different enlarged views of the deployment mechanism103. Deployment mechanism 103 may be made of any material that issuitable for use in medical devices. For example, deployment mechanism103 may be made of a lightweight aluminum or a biocompatible plasticmaterial. Examples of such suitable plastic materials includepolycarbonate and other polymeric resins such as DELRIN and ULTEM. Incertain embodiments, deployment mechanism 103 is made of a material thatmay be autoclaved, and thus allow for deployment mechanism 103 to bere-usable. Alternatively, device 100 may be sold as a one-time-usedevice, and thus the material of the deployment mechanism does not needto be a material that is autoclavable.

Deployment mechanism 103 includes a distal portion 109 and a proximalportion 110. The deployment mechanism 103 is configured such that distalportion 109 is movable within proximal portion 110. More particularly,distal portion 109 is capable of partially retracting to within proximalportion 110.

In this embodiment, the distal portion 109 is shown to taper to aconnection with a hollow shaft 104. This embodiment is illustrated suchthat the connection between the hollow shaft 104 and the distal portion109 of the deployment mechanism 103 occurs inside the housing 101. Inother embodiments, the connection between hollow shaft 104 and theproximal portion 109 of the deployment mechanism 103 may occur outsideof the housing 101. Hollow shaft 104 may be removable from the distalportion 109 of the deployment mechanism 103. Alternatively, the hollowshaft 104 may be permanently coupled to the distal portion 109 of thedeployment mechanism 103.

Generally, hollow shaft 104 is configured to hold an intraocular shunt,such as the intraocular shunts according to some embodiments. The shaft104 may be any length. A usable length of the shaft may be anywhere fromabout 5 mm to about 40 mm, and is 15 mm in certain embodiments. Incertain embodiments, the shaft is straight. In other embodiments, shaftis of a shape other than straight, for example a shaft having a bendalong its length.

A proximal portion of the deployment mechanism includes optional grooves116 to allow for easier gripping by an operator for easier rotation ofthe deployment mechanism, which will be discussed in more detail below.The proximal portion 110 of the deployment mechanism also includes atleast one indicator that provides feedback to an operator as to thestate of the deployment mechanism. The indicator may be any type ofindicator known in the art, for example a visual indicator, an audioindicator, or a tactile indicator. FIGS. 18A-18D shows a deploymentmechanism having two indicators, a ready indicator 111 and a deployedindicator 119. Ready indicator 111 provides feedback to an operator thatthe deployment mechanism is in a configuration for deployment of anintraocular shunt from the deployment device 100. The ready indicator111 is shown in this embodiment as a green oval having a triangle withinthe oval. Deployed indicator 119 provides feedback to the operator thatthe deployment mechanism has been fully engaged and has deployed theshunt from the deployment device 100. The deployed indicator 119 isshown in this embodiment as a yellow oval having a black square withinthe oval. The indicators are located on the deployment mechanism suchthat when assembled, the indicators 111 and 119 may be seen through slot106 in housing 101.

The proximal portion 110 includes a stationary portion 110 b and arotating portion 110 a. The proximal portion 110 includes a channel 112that runs part of the length of stationary portion 110 b and the entirelength of rotating portion 110 a. The channel 112 is configured tointeract with a protrusion 117 on an interior portion of housingcomponent 101 a (FIGS. 19A and 19B). During assembly, the protrusion 117on housing component 101 a is aligned with channel 112 on the stationaryportion 110 b and rotating portion 110 a of the deployment mechanism103. The proximal portion 110 of deployment mechanism 103 is slid withinhousing component 101 a until the protrusion 117 sits within stationaryportion 110 b (FIG. 19C). Assembled, the protrusion 117 interacts withthe stationary portion 110 b of the deployment mechanism 103 andprevents rotation of stationary portion 110 b. In this configuration,rotating portion 110 a is free to rotate within housing component 101 a.

Referring back to FIGS. 18A-18D, the rotating portion 110 a of proximalportion 110 of deployment mechanism 103 also includes channels 113 a,113 b, and 113 c. Channel 113 a includes a first portion 113 a 1 that isstraight and runs perpendicular to the length of the rotating portion110 a, and a second portion 113 a 2 that runs diagonally along thelength of rotating portion 110 a, downwardly toward a proximal end ofthe deployment mechanism 103. Channel 113 b includes a first portion 113b 1 that runs diagonally along the length of the rotating portion 110 a,downwardly toward a distal end of the deployment mechanism 103, and asecond portion that is straight and runs perpendicular to the length ofthe rotating portion 110 a. The point at which first portion 113 a 1transitions to second portion 113 a 2 along channel 113 a, is the sameas the point at which first portion 113 b 1 transitions to secondportion 113 b 2 along channel 113 b. Channel 113 c is straight and runsperpendicular to the length of the rotating portion 110 a. Within eachof channels 113 a, 113 b, and 113 c, sit members 114 a, 114 b, and 114 crespectively. Members 114 a, 114 b, and 114 c are movable withinchannels 113 a, 113 b, and 113 c. Members 114 a, 114 b, and 114 c alsoact as stoppers that limit movement of rotating portion 110 a, whichthereby limits axial movement of the shaft 104.

FIG. 20 shows a cross-sectional view of deployment mechanism 103. Member114 a is connected to the distal portion 109 of the deployment mechanism103. Movement of member 114 a results in retraction of the distalportion 109 of the deployment mechanism 103 to within the proximalportion 110 of the deployment mechanism 103. Member 114 b is connectedto a pusher component 118. The pusher component 118 extends through thedistal portion 109 of the deployment mechanism 103 and extends into aportion of hollow shaft 104. The pusher component is involved indeployment of a shunt from the hollow shaft 104. An exemplary pushercomponent is a plunger. Movement of member 114 b engages pusher 118 andresults in pusher 118 advancing within hollow shaft 104.

Reference is now made to FIGS. 21A-23D, which accompany the followingdiscussion regarding deployment of a shunt 115 from deployment device100. FIG. 21A shows deployment device 100 in a pre-deploymentconfiguration. In this configuration, shunt 115 is loaded within hollowshaft 104 (FIG. 21C). As shown in FIG. 21C, shunt 115 is only partiallywithin shaft 104, such that a portion of the shunt is exposed. However,the shunt 115 does not extend beyond the end of the shaft 104. In otherembodiments, the shunt 115 is completely disposed within hollow shaft104. The shunt 115 is loaded into hollow shaft 104 such that the shuntabuts pusher component 118 within hollow shaft 104. A distal end ofshaft 104 is beveled to assist in piercing tissue of the eye.

Additionally, in the pre-deployment configuration, a portion of theshaft 104 extends beyond the sleeve 105 (FIG. 21C). The deploymentmechanism is configured such that member 114 a abuts a distal end of thefirst portion 113 a 1 of channel 113 a, and member 114 b abut a proximalend of the first portion 113 b 1 of channel 113 b (FIG. 21B). In thisconfiguration, the ready indicator 111 is visible through slot 106 ofthe housing 101, providing feedback to an operator that the deploymentmechanism is in a configuration for deployment of an intraocular shuntfrom the deployment device 100 (FIG. 21A). In this configuration, thedevice 100 is ready for insertion into an eye (insertion configurationor pre-deployment configuration). Methods for inserting and implantingshunts are discussed in further detail below.

Once the device has been inserted into the eye and advanced to alocation to where the shunt will be deployed, the shunt 115 may bedeployed from the device 100. The deployment mechanism 103 is atwo-stage system. The first stage is engagement of the pusher component118 and the second stage is retraction of the distal portion 109 towithin the proximal portion 110 of the deployment mechanism 103.Rotation of the rotating portion 110 a of the proximal portion 110 ofthe deployment mechanism 103 sequentially engages the pusher componentand then the retraction component.

In the first stage of shunt deployment, the pusher component is engagedand the pusher partially deploys the shunt from the deployment device.During the first stage, rotating portion 110 a of the proximal portion110 of the deployment mechanism 103 is rotated, resulting in movement ofmembers 114 a and 114 b along first portions 113 a 1 and 113 b 1 inchannels raand 113 b. Since the first portion 113 a 1 of channel 113 ais straight and runs perpendicular to the length of the rotating portion110 a, rotation of rotating portion 110 a does not cause axial movementof member 114 a. Without axial movement of member 114 a, there is noretraction of the distal portion 109 to within the proximal portion 110of the deployment mechanism 103. Since the first portion 113 b 1 ofchannel 113 b runs diagonally along the length of the rotating portion110 a, upwardly toward a distal end of the deployment mechanism 103,rotation of rotating portion 110 a causes axial movement of member 114 btoward a distal end of the device. Axial movement of member 114 b towarda distal end of the device results in forward advancement of the pushercomponent 118 within the hollow shaft 104. Such movement of pushercomponent 118 results in partially deployment of the shunt 115 from theshaft 104.

FIGS. 22A-22C show schematics of the deployment mechanism at the end ofthe first stage of deployment of the shunt from the deployment device.As is shown FIG. 22A, members 114 a and 114 b have finished traversingalong first portions 113 a 1 and 113 b 1 of channels 113 a and 113 b.Additionally, pusher component 118 has advanced within hollow shaft 104(FIG. 22B), and shunt 115 has been partially deployed from the hollowshaft 104 (FIG. 22C). As is shown in these figures, a portion of theshunt 115 extends beyond an end of the shaft 104.

In the second stage of shunt deployment, the retraction component isengaged and the distal portion of the deployment mechanism is retractedto within the proximal portion of the deployment mechanism, therebycompleting deployment of the shunt from the deployment device. Duringthe second stage, rotating portion 110 a of the proximal portion 110 ofthe deployment mechanism 103 is further rotated, resulting in movementof members 114 a and 114 b along second portions 113 a 2 and 113 b 2 inchannels 113 a and 113 b. Since the second portion 113 b 2 of channel113 b is straight and runs perpendicular to the length of the rotatingportion 110 a, rotation of rotating portion 110 a does not cause axialmovement of member 114 b. Without axial movement of member 114 b, thereis no further advancement of pusher 118. Since the second portion 113 a2 of channel 113 a runs diagonally along the length of the rotatingportion 110 a, downwardly toward a proximal end of the deploymentmechanism 103, rotation of rotating portion 110 a causes axial movementof member 114 a toward a proximal end of the device. Axial movement ofmember 114 a toward a proximal end of the device results in retractionof the distal portion 109 to within the proximal portion 110 of thedeployment mechanism 103. Retraction of the distal portion 109, resultsin retraction of the hollow shaft 104. Since the shunt 115 abuts thepusher component 118, the shunt remains stationary as the hollow shaft104 retracts from around the shunt 115 (FIG. 22C). The shaft 104retracts almost completely to within the sleeve 105. During both stagesof the deployment process, the sleeve 105 remains stationary and in afixed position.

FIGS. 23A-23D show schematics of the device 100 after deployment of theshunt 115 from the device 100. FIG. 23B shows a schematic of thedeployment mechanism at the end of the second stage of deployment of theshunt from the deployment device. As is shown in FIG. 23B, members 114 aand 114 b have finished traversing along second portions 113 a 2 and 113b 2 of channels 113 a and 113 b. Additionally, distal portion 109 hasretracted to within proximal portion 110, thus resulting in retractionof the hollow shaft 104 to within the sleeve 105. FIG. 23D shows anenlarged view of the distal portion of the deployment device afterdeployment of the shunt. This figure shows that the hollow shaft 104 isnot fully retracted to within the sleeve 105 of the deployment device100. However, in certain embodiments, the shaft 104 may completelyretract to within the sleeve 105.

Additional Methods for Intrascleral Shunt Placement

Some embodiments of the methods disclosed herein can involve creating anopening in the sclera (e.g., by piercing the sclera with a deliverydevice), and positioning a shunt in the anterior chamber of the eye suchthat the shunt terminates adjacent an opening formed in the sclera. Insome embodiments, such placement can permit flow through the shunt toreach the intrascleral space, thereby facilitating fluid flow throughboth the opening and the intrascleral space. The outlet of the shunt maybe positioned in different places within the intrascleral space. Forexample, the outlet of the shunt may be positioned within the sclera(e.g., within deep and superficial layers or tissue of the sclera).Alternatively, the outlet of the shunt may be positioned such that theoutlet is even with or superficial to the opening through the sclera.

Methods of implanting intraocular shunts are known in the art. Shuntsmay be implanted using an ab externo approach (entering through theconjunctiva and inwards through the sclera) or an ab interno approach(entering through the cornea, across the anterior chamber, through thetrabecular meshwork and sclera). The deployment device may be any devicethat is suitable for implanting an intraocular shunt into an eye. Suchdevices generally include a shaft connected to a deployment mechanism.In some devices, a shunt is positioned over an exterior of the shaft andthe deployment mechanism works to deploy the shunt from an exterior ofthe shaft. In other devices, the shaft is hollow and the shunt is atleast partially disposed in the shaft. In those devices, the deploymentmechanism works to deploy the shunt from within the shaft. Depending onthe device, a distal portion of the shaft may be sharpened or blunt, orstraight or curved.

Ab-Interno Approach

Ab interno approaches for implanting an intraocular shunt in thesubconjunctival space are shown for example in Yu et al. (U.S. Pat. No.6,544,249 and U.S. Patent Publication No. 2008/0108933) and Prywes (U.S.Pat. No. 6,007,511), the contents of each of which are incorporated byreference herein in its entirety. An exemplary ab-interno method employsa transpupil approach and involves creating a first opening in thesclera of an eye, advancing a shaft configured to hold an intraocularshunt across an anterior chamber of an eye and through the sclera tocreate a second opening in the sclera, retracting the shaft through thesecond opening to within the sclera (i.e., the intrascleral space),deploying the shunt from the shaft such that the shunt forms a passagefrom the anterior chamber of the eye to the intrascleral space of theeye, such that an outlet of the shunt is positioned so that at leastsome of the fluid that exits the shunt flows through the second openingin the sclera, and withdrawing the shaft from the eye. The first openingin the sclera may be made in any manner. In certain embodiments, theshaft creates the first opening in the sclera. In other embodiments, atool other than the shaft creates the first opening in the sclera.

In certain embodiments, some embodiments of the methods disclosed hereincan generally involve inserting into the eye a hollow shaft configuredto hold an intraocular shunt. In certain embodiments, the hollow shaftis a component of a deployment device that may deploy the intraocularshunt. The shunt is then deployed from the shaft into the eye such thatthe shunt forms a passage from the anterior chamber into the sclera(i.e., the intrascleral space). The hollow shaft is then withdrawn fromthe eye.

To place the shunt within the eye, a surgical intervention to implantthe shunt is performed that involves inserting into the eye a deploymentdevice that holds an intraocular shunt, and deploying at least a portionof the shunt within intrascleral space. FIGS. 24-31 provide an exemplarysequence for ab interno shunt placement. In certain embodiments, ahollow shaft 209 of a deployment device holding the shunt 212 enters theeye through the cornea (ab interno approach, FIG. 24). The shaft 209 isadvanced across the anterior chamber 210 in what is referred to as atranspupil implant insertion. The shaft 209 is advanced through theanterior angle tissues of the eye and into the sclera 8 and furtheradvanced until it passes through the sclera 8, thereby forming a secondopening in the sclera 8 (FIGS. 25-26). Once the second opening in thesclera 8 is achieved, the shaft 209 is retracted all the way backthrough the sclera 8 and into the anterior chamber 210 of the eye (FIGS.27-30). During this shaft retraction, the shunt 212 is held in place bya plunger rod 211 that is positioned behind the proximal end of theshunt 212. After the shaft 209 has been completely withdrawn from thesclera 8, the plunger rod 211 is withdrawn as well and the shuntimplantation sequence is complete (FIG. 31). This process results in animplanted shunt 212 in which a distal end of the shunt 212 is proximatea passageway 214 through the sclera 8. Once fully deployed, a proximalend of shunt 212 resides in the anterior chamber 210 and a distal end ofshunt 212 resides in the intrascleral space. Preferably a sleeve 213 isused around the shaft 212 and designed in length such that the sleeve213 acts as a stopper for the scleral penetration of the shaft and alsodetermines the longitudinal placement of the proximal end of the shunt.

Insertion of the shaft of the deployment device into the sclera 8produces a long scleral channel of about 2 mm to about 5 mm in length.Withdrawal of the shaft of the deployment device prior to deployment ofthe shunt 212 from the device produces a space in which the shunt 212may be deployed. Deployment of the shunt 212 allows for aqueous humor 3to drain into traditional fluid drainage channels of the eye (e.g., theintrascleral vein, the collector channel, Schlemm's canal, thetrabecular outflow, and the uveoscleral outflow to the ciliary muscle.The deployment is performed such that an outlet of the shunt ispositioned proximate the opening in the sclera so that at least some ofthe fluid that exits the shunt flows through the opening in the sclera,thereby ensuring that the intrascleral space does not become overwhelmedwith fluid output from the shunt.

Preferably, some embodiments of the methods disclosed herein areconducted by making an incision in the eye prior to insertion of thedeployment device. In some embodiments of the methods disclosed hereinmay be conducted without making an incision in the eye prior toinsertion of the deployment device. In certain embodiments, the shaftthat is connected to the deployment device has a sharpened point or tip.In certain embodiments, the hollow shaft is a needle. Exemplary needlesthat may be used are commercially available from Terumo Medical Corp.(Elkington Md). In some embodiments, the needle has a hollow interiorand a beveled tip, and the intraocular shunt is held within the hollowinterior of the needle. In another embodiment, the needle has a hollowinterior and a triple ground point or tip.

Some embodiments of the methods disclosed herein are preferablyconducted without needing to remove an anatomical portion or feature ofthe eye, including but not limited to the trabecular meshwork, the iris,the cornea, or aqueous humor. Some embodiments of the methods disclosedherein are also preferably conducted without inducing substantial ocularinflammation, such as subconjunctival blebbing or endophthalmitis. Suchmethods can be achieved using an ab interno approach by inserting thehollow shaft configured to hold the intraocular shunt through thecornea, across the anterior chamber, through the trabecular meshwork andinto the sclera. However, some embodiments of the methods disclosedherein may be conducted using an ab externo approach.

When some embodiments of the methods disclosed herein are conductedusing an ab interno approach, the angle of entry through the cornea aswell as the up and downward forces applied to the shaft during thescleral penetration affect optimal placement of the shunt in theintrascleral space. Preferably, the hollow shaft is inserted into theeye at an angle superficial to the corneal limbus, in contrast withentering through or deep to the corneal limbus. For example, the hollowshaft is inserted about 0.25 mm to about 3.0 mm, preferably about 0.5 mmto about 2.5 mm, more preferably about 1.0 mm to about 2.0 mmsuperficial to the corneal limbus, or any specific value within saidranges, e.g., about 1.0 mm, about 1.1 mm, about 1.2 mm, about 1.3 mm,about 1.4 mm, about 1.5 mm, about 1.6 mm, about 1.7 mm, about 1.8 mm,about 1.9 mm, or about 2.0 mm superficial to the corneal limbus.

Without intending to be bound by any theory, placement of the shuntfarther from the limbus at the exit site, as provided by an angle ofentry superficial to the limbus, as well as an S-shaped scleral tunnel(FIG. 32) due to applied up or downward pressure during the scleralpenetration of the shaft is believed to provide access to more lymphaticchannels for drainage of aqueous humor, such as the episcleral lymphaticnetwork, in addition to the conjunctival lymphatic system.

Ab Externo Approach

In other embodiments, an ab externo approach is employed. Ab externoimplantation approaches are shown for example in Nissan et al. (U.S.Pat. No. 8,109,896), Tu et al. (U.S. Pat. No. 8,075,511), and Haffner etal. (U.S. Pat. No. 7,879,001), the content of each of which isincorporated by reference herein in its entirety. An exemplary abexterno approach avoids having to make a scleral flap. In this preferredembodiment, a distal end of the deployment device is used to make anopening into the eye and into the sclera. For example, a needle isinserted from ab externo through the sclera and exits the anterior angleof the eye. The needle is then withdrawn, leaving a scleral slit behind.A silicone tube with sufficient stiffness is then manually pushedthrough the scleral slit from the outside so that the distal tube endsdistal to the Trabecular Meshwork in the anterior chamber of the eye.Towards the proximal end, the tube exits the sclera, lays on top of it,and connects on its proximal end to a plate that is fixated by suturesto the outside scleral surface far away (>10 mm) from the limbus.

FIGS. 33-39 describes another ab externo method that uses a deploymentdevice. In this method, a distal portion of the deployment deviceincludes a hollow shaft 209 that has a sharpened tip (FIG. 33). A shunt212 resides within the shaft 209. The distal shaft 209 is advanced intothe eye and into the sclera 8 until a proximal portion of the shaftresides in the anterior chamber 210 and a distal portion of the shaft209 is inside the scleral 8 (FIGS. 34-36). Deployment of the shunt 212that is located inside the shaft 209 is then accomplished by a mechanismthat withdraws the shaft 209 while the shunt 212 is held in place by aplunger 211 behind the proximal end of the shunt 212 (FIGS. 37-39). Asthe implantation sequence progresses, the shaft 209 is completelywithdrawn from the sclera 8. After that, the plunger 211 is withdrawnfrom the sclera 8, leaving the shunt 212 behind with its distal endinside the sclera 8, its proximal end inside the anterior chamber 210,and a passageway 214 through the sclera 8. In a preferred embodiment theshaft 209 is placed inside a sleeve 213 that is dimensioned in lengthrelative to the shaft 209 such that it will act as stopper during thepenetration of the shaft 209 into the eye and at the same time assurescontrolled longitudinal placement of the shunt 212 relative to the outersurface of the eye. The sleeve 213 may be beveled to match theanatomical angle of the entry site surface.

The shaft penetrates the conjunctival layer before it enters andpenetrates the sclera. This causes a conjunctival hole that could createa fluid leakage after the shunt placement has been completed. Tominimize the chance for any leakage, a small diameter shaft is used thatresults in a self-sealing conjunctival wound. To further reduce thechance for a conjunctival leak, a suture can be placed in theconjunctiva around the penetration area after the shunt placement.

Furthermore the preferred method of penetrating the conjunctiva isperformed by shifting the conjunctival layers from posterior to thelimbus towards the limbus, using e.g. an applicator such as a Q-tip,before the shaft penetration is started. This is illustrated in FIGS.40-41. That figure shows that an applicator 257 is put onto theconjunctiva 258, about 6 mm away from the limbus. The loose conjunctivalayer is then pushed towards the limbus to create folding tissue layersthat are about 2 mm away from the limbus. The device shaft 209 is nowinserted through the conjunctiva and sclera 8 starting about 4 mm awayfrom the limbus. After the shunt placement has been completed, the Q-tipis released and the conjunctival perforation relaxes back from about 4mm to about 8 mm limb at distance. This can cause the conjunctivalperforation to be 4 mm away from the now slowly starting drainage exit.This distance will reduce any potential for leakage and allows for afaster conjunctival healing response. Alternative to this describedupward shift, a sideway shift of the conjunctiva or anything in betweenis feasible as well. In another embodiment of the ab externo method, aconjunctival slit is cut and the conjunctiva is pulled away from theshaft entry point into the sclera. After the shunt placement iscompleted, the conjunctival slit is closed again through sutures.

In certain embodiments, since the tissue surrounding the trabecularmeshwork is optically opaque, an imaging technique, such as ultrasoundbiomicroscopy (UBM), optical coherence tomography (OCT) or a laserimaging technique, can be utilized. The imaging can provide guidance forthe insertion of the deployment device and the deployment of the shunt.This technique can be used with a large variety of shunt embodimentswith slight modifications since the trabecular meshwork is puncturedfrom the scleral side, rather than the anterior chamber side, in the abexterno insertion.

In another ab externo approach, a superficial flap may be made in thesclera and then a second deep scleral flap may be created and excisedleaving a scleral reservoir under the first flap. Alternatively, asingle scleral flap may be made with or without excising any portion ofthe sclera.

A shaft of a deployment device is inserted under the flap and advancedthrough the sclera and into an anterior chamber. The shaft is advancedinto the sclera until a proximal portion of the shaft resides in theanterior chamber and a distal portion of the shaft is in proximity tothe trabecular outflow. The deployment is then performed such that anoutlet of the shunt is positioned proximate the second opening in thesclera so that at least some of the fluid that exits the shunt flowsthrough the first opening in the sclera, thereby ensuring that theintrascleral space does not become overwhelmed with fluid output fromthe shunt. At the conclusion of the ab externo implantation procedure,the scleral flap may be sutured closed. The procedure also may beperformed without suturing.

Regardless of the implantation method employed, some embodiments of themethods disclosed herein recognize that the proximity of the distal endof the shunt to the scleral exit slit affects the flow resistancethrough the shunt, and therefore affects the intraocular pressure in theeye. For example, if the distal end of the shunt 212 is flush with thesclera surface then there is no scleral channel resistance (FIG. 42). Inthis embodiment, total resistance comes from the shunt 212 alone. Inanother embodiment, if the distal end of the shunt 212 is about 200 μmto about 500 μm behind the scleral exit, then the scleral slit closespartially around the exit location, adding some resistance to theoutflow of aqueous humor (FIG. 43). In another embodiments, if thedistal end of the shunt 212 is more than about 500 microns behind thescleral exit, than the scleral slit closes completely around the exitlocation with no backpressure and opens gradually to allow aqueous humorto seep out when the intraocular pressure raises e.g. above 10 mmHg(FIG. 44). The constant seepage of aqueous humor keeps the scleral slitfrom scaring closed over time.

Effectively, shunt placement according to some embodiments of themethods disclosed herein achieve a valve like performance where thescleral slit in front of the distal shunt end acts like a valve. Theopening (cracking) pressure of this valve can be adjusted by the outershunt diameter and its exact distal end location relative to the scleralexit site. Typical ranges of adjustment are 1 mmHg to 20 mmHg. Thispassageway distance can be controlled and adjusted through the design ofthe inserting device as well as the shunt length and the deploymentmethod. Therefore a specific design can be chosen to reduce or preventhypotony (<6 mmHg) as a post-operative complication.

Incorporation by Reference

References and citations to other documents, such as patents, patentapplications, patent publications, journals, books, papers, webcontents, have been made throughout this disclosure. All such documentsare hereby incorporated herein by reference in their entirety for allpurposes.

Equivalents

It is understood that the specific order or hierarchy of steps in theprocesses disclosed is an illustration of exemplary approaches. Basedupon design preferences, it is understood that the specific order orhierarchy of steps in the processes may be rearranged. Some of the stepsmay be performed simultaneously. The accompanying method claims presentelements of the various steps in a sample order, and are not meant to belimited to the specific order or hierarchy presented.

Terms such as “top,” “bottom,” “front,” “rear” and the like as used inthis disclosure should be understood as referring to an arbitrary frameof reference, rather than to the ordinary gravitational frame ofreference. Thus, a top surface, a bottom surface, a front surface, and arear surface may extend upwardly, downwardly, diagonally, orhorizontally in a gravitational frame of reference.

Furthermore, to the extent that the term “include,” “have,” or the likeis used in the description or the claims, such term is intended to beinclusive in a manner similar to the term “comprise” as “comprise” isinterpreted when employed as a transitional word in a claim.

The word “exemplary” is used herein to mean “serving as an example,instance, or illustration.” Any embodiment described herein as“exemplary” is not necessarily to be construed as preferred oradvantageous over other embodiments.

A reference to an element in the singular is not intended to mean “oneand only one” unless specifically stated, but rather “one or more.”Pronouns in the masculine (e.g., his) include the feminine and neutergender (e.g., her and its) and vice versa. The term “some” refers to oneor more. Underlined and/or italicized headings and subheadings are usedfor convenience only, do not limit the subject technology, and are notreferred to in connection with the interpretation of the description ofthe subject technology. All structural and functional equivalents to theelements of the various configurations described throughout thisdisclosure that are known or later come to be known to those of ordinaryskill in the art are expressly incorporated herein by reference andintended to be encompassed by the subject technology. Moreover, nothingdisclosed herein is intended to be dedicated to the public regardless ofwhether such disclosure is explicitly recited in the above description.

While certain aspects and embodiments of the inventions have beendescribed, these have been presented by way of example only, and are notintended to limit the scope of the inventions. Indeed, the novel methodsand systems described herein may be embodied in a variety of other formswithout departing from the spirit thereof. The accompanying claims andtheir equivalents are intended to cover such forms or modifications aswould fall within the scope and spirit of the inventions.

What is claimed is:
 1. A method comprising inserting, through a cornea,an implant in an eye having (i) an anterior chamber and (ii) a sclera,to form a channel through the sclera and thereby establish fluidcommunication between the anterior chamber and the channel, andadministering a pharmaceutical or biological agent to the eye.